System, device and method for ablation of a vessel&#39;s wall from the inside

ABSTRACT

The current invention concerns systems, devices and methods for the ablation of a vessel&#39;s wall from the inside, more specifically to implant devices and to the ablation of the wall of one or more pulmonary veins (PV) from the inside, preferably transmural ablation and preferably at the level of the antrum. Hereby, one or more implant devices can be implanted in the vessels and can subsequently be heated by external energy-providing means.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is the U.S. National Phase under 35 U.S.C. §371 ofInternational Application PCT/EP2012/055999, filed Apr. 2, 2012, whichclaims priority to PCT/IB2011/051411, filed Apr. 1, 2011 andPCT/EP2011/058587, filed May 25, 2011.

TECHNICAL FIELD

The invention pertains to the technical field of the treatment of bodilyvessels by means of ablation, more specifically to the treatment ofcardiac conditions such as atrial fibrillation (AF). In particular, thepresent invention relates to systems, devices and methods for theablation of a vessel's wall from the inside, more specifically toimplant devices and to the ablation of the wall of one or more pulmonaryveins (PV) from the inside, preferably transmural ablation andpreferably at the level of the antrum.

BACKGROUND

The present invention concerns a system of one or more implant devicesand excitation device, an implant device and a method using the systemand one or more devices for the treatment of arterial and venousstructures.

The present invention also concerns implant devices, a system of implantdevices and external excitation means, and a method for positioning oneor more implant devices in a vessel, and subsequently heating theseimplant devices, preferably simultaneously, thereby transferring heatfrom implant devices to the vessel's inner wall.

The system, device and method can for example be used for treatingatrial arrhythmias, more specific atrial fibrillation (AF), morespecific paroxysmal, persistent or permanent. More specifically thisinvention describes a method that allows to repeatedly create lesions inthe heart, more specifically in the atria, more specifically in the leftand right atrium, more specifically in the antrum or ostium of thepulmonary veins (PVs). Hereby, the general concept is to implant one ormore implant devices into the PVs or other vessels, said implant devicesmaking contact with the vessels' inner walls at the positions whereablation is deemed necessary in order to have PV isolation (PVI). Incontrast with prior art, ablation is not performed immediately, but theone or more implant devices can be heated up to a specified temperatureby external energy-providing means, which are spatially separated from,i.e. not touching, the implant device and able to provide energyremotely to the implant device for increasing the temperature of theablation region of the implant device up to an ablation temperature. Ina preferred embodiment, an implant device comprises an area which ismade from a material which may show magnetic hysteresis and the externalenergy-providing means are able to create a time-varying magnetic fieldat the position of the implanted device, hereby heating the implantthrough the phenomenon of magnetic hysteresis. The maximum temperaturethe implant device can reach, is limited by the Curie or Néeltemperature of the magnetic material used, above which temperature themagnetic hysteresis effect disappears. This Curie or Néel temperaturecan be engineered precisely to the necessary ablation temperature e.g.by changing the composition of the magnetic alloy that is used. Inanother embodiment, non-magnetic material may be used, and insulationmaterial may then be used to provide sufficient temperature-controllingmeans. In an embodiment, the heating of the implant device is done byJoule heating or direct heating, or any other heating system.

The implant device according to the present invention can thus be usedinside the heart, both the right and the left side, inside the pulmonaryveins, but also if necessary, in arterial and venous structures outsidethe heart.

Indeed, the system, device and method according to the present inventioncan also be used to perform ablation throughout the renal arteries, toperform ablation of the nervous system surrounding the renal arteries,to perform ablation of the renal sympathetic nerves, more specific toperform ablation of the renal sympathetic nerves in the adventitiasurrounding the renal arteries, to perform ablation of renal afferentand/or efferent nerves.

The device can be used in the renal arteries in which case the device,system and method can be used to treat arterial hypertension,norepinephrine spillover, heart failure, hypertension related targetorgan damage, etc.

The device can be used in the renal arteries in which case the device,system and method can be used to treat arterial hypertension, morespecific, but not limited to, mild, moderate and/or severe hypertension,masked hypertension, white-coat hypertension, reverse dippinghypertension, non-dipping hypertension, dipping hypertension endneuroadrenergic hypertension.

The devices, systems and methods as described in this document may alsobe used in human or animal corpses or in models of human or animalbodies, e.g. for practicing or educational purposes, whereby the heatingof the implant devices leaves ablation marks on the vessel's inner wallwhich can be used to check if the implant devices were positionedcorrectly and sufficient ablation occurred.

The present document focuses its description on the application of thedevice inside the heart, both the right and the left side, and insidethe pulmonary veins.

A person skilled in the art will be able to interpret the device, thesystem and the method and to provide them of specific features,components or steps if to be used in other areas.

Human wellbeing is menaced by numerous disorders which change with time.The art of medicine continuously needs to innovate and to adapt to thesechanges. Despite incessant therapeutic improvements, cardiac diseaseremains the most important cause of death and hospitalizations in thewestern society.

Atrial fibrillation, often referred to as AF, is an arrhythmia of theheart causing irregular electrical activity, followed by disorganizedand ineffective contractions.

Patients experiencing AF suffer from palpitations, fatigue, severedecrease in quality of life, worsening of heart failure, cerebralstroke, increased mortality and many other symptoms.

Prevalence and incidence of AF is gradually increasing thus causing AFto reach epidemic proportions.

So far, anti-arrhythmic drug treatment for AF is characterized by twomajor findings: inefficacy and/or intolerable side effects.

The currently available and commonly used drugs to prevent or cure AFcan be divided into two groups.

The first group consist of the so-called class-I drugs, betablockers,dronedarone and sotalol.

These drugs have a rather low efficiency ranging between 20 to 40%.Initiating and continuing these drugs requires close monitoring of thepatient as these drugs in itself can easily induce life threateningarrhythmias.

The second group consists of only one drug, namely amiodarone, which isthe most potent available drug to treat AF.

Its efficiency can range up to 65%. However, the list of possible sideeffects is practically unlimited: severe thyroid problems, severe lungdisease, irreversible tinting of the skin, visual defects, possiblecarcinogenic nature, etc.

Recently a new invasive treatment modality for atrial fibrillation wasdiscovered when the Bordeaux group of Prof. Dr. Haissaguerre found thepulmonary veins, often referred to as PV's, to be the location of thetrigger for AF.

In the following years various techniques were developed to encircle thePV's as an alternative to pharmacological therapy for treating AF.

This technique is called pulmonary vein isolation, often abbreviated asPVI.

The aim was to electrically isolate the triggers in the PV's, assuringnot a single electrical connection between the PV's and the left atriumremained.

Soon enough, it was discovered that even a small gap of for example 1 mmin the line encircling the PV's could lead to electrical reconnection ofthe PV's and hence failure of the procedure with reoccurrence of AF.

Electrophysiology, the art of treating cardiac arrhythmias, ischaracterized by the use of high-tech equipment to perform diagnosticand therapeutic interventions inside the heart.

Nowadays it is possible to successfully treat virtually every arrhythmiaby means of a percutaneous intervention. Nevertheless, curing a patientfrom AF in a safe and effective manner remains a big hurdle inelectrophysiology.

There are two types of procedures by which a PVI can be achieved.

The first group consists of technologies and devices built to encirclethe PV's point by point, making sure a continuous line is formed withoutany gaps.

In most cases a combination is used of a non-fluoroscopic technique tovisualize the left atrium with its PV's and a catheter capable ofdelivering radiofrequency (RF) or cryo-energy.

However, with this first group of procedures, it is not alwaysguaranteed that a continuous line is formed with any gaps. This canoccur because the pressure with which an ablating tip is pressed againstthe wall, the amount of energy transferred from the ablating tip to thewall, the size of the ablation spot on the vessel wall, etc. is notcompletely under control. In some cases, a gap of the order of 1 mm mayalready be too wide to ensure a successful outcome of the PVI procedure.In these cases, a repetition of the whole procedure with theaccompanying danger, discomfort, cost, etc. for the patient, is usuallydeemed necessary.

The other group consists of devices created to perform PVI in ‘onesingle shot’ consecutively in each of the four PV's.

A whole assortment of catheters or sheaths has been conceived: ballooncatheters delivering cryo-energy, laser energy, high intensity focusedultrasound, thermal energy, circular catheters delivering pulsed wave RFenergy, basket-like catheters delivering RF energy, etc.

PVI has grown from an experimental therapy to a state-of-the-artintervention that can possibly cure AF.

Acute success rates in paroxysmal AF can reach 90% in the most optimalcircumstances, with a complication rate around 6%. The most commoncomplication of PVI is cardiac tamponade due to perforation of the leftatrium by the ablation catheter.

Usually this can be dealt with by performing a percutaneous puncture ofthe pericardium with evacuation of the blood, if this proves to beinadequate, a surgical intervention by means of thoracotomy is needed.

The most feared and usually lethal complication is development of afistula between the oesophagus and the left atrium.

In the past 10 years, catheter ablation techniques in patients with AFhave evolved from an initial approach focused on the PV's and theirjunctions with the left atrium, further often abbreviated as LA, to amore extensive intervention, mainly, but not exclusively, on the LAmyocardium and its neuro-vegetative innervation.

It is now recognized that the cornerstone of most catheter and surgicalablation approaches is to isolate the PV's electrically from the LA.

Despite more or less substantial differences among the various cathetertechniques that are currently utilized worldwide, results seem to beuniformly similar, with success rates in the range from 50% to 90%depending on the patients and their type of AF (permanent, long-standingpersistent, short-standing persistent, or paroxysmal AF).

Frequently a second AF ablation procedure is necessary to improveprocedural outcome.

Procedural time to perform a PVI has evolved a great deal in the pastyears. Initially, point by point PVI regularly could take more than 6hours.

New imaging techniques shortened these laborious procedures to aboutfour to six hours.

The ‘single-shot’ procedures again are somewhat shorter, but still taketwo to three hours of procedural time in general.

Fluoroscopy time needed to perform these procedures has equallydecreased, but overall ranges between 20-40 minutes.

Because of major discomfort for the patient and the need for the patientto remain motionless during the whole procedure, PVI is performed undergeneral anesthesia in many centers around the world.

The other centers use ‘conscious sedation’ which means the patient issedated with several different drugs but without the intention tointubate and ventilate the patient.

The need to sedate the patient can cause different harmful side effects.

First of all, general anesthesia always carries a certain mortality riskfor the patient. Good ‘conscious sedation’ on the other hand is hard toaccomplish.

Under-dosing the drugs leads to patient discomfort and unsolicitedpatient movement.

Over-dosing the drugs can necessitate switching to general anesthesiaduring the procedure, which is far from obvious and can even bedangerous in many cases.

The present invention has the intention to conceive a technique which ismore acceptable for the patient, less time-consuming, safer and at leastequally efficacious in performing PVI.

U.S. Pat. No. 6,632,223 discloses a system for treating atrialfibrillation comprising a stent and a catheter able to deliver the stentnear the treatment site. The stent is self-expanding and, oncedelivered, expands to lodge against the interior wall of the pulmonaryvein. The stent can be heated by sending a current through electricalwires in the catheter which are connected to the stent. The thus heatedstent may ablate a circumferential blocking lesion of the PV wall. Theablation occurs while the catheter is physically connected to the stent.Therefore, after the ablation, the stent may be disconnected from thecatheter and remain in place e.g. to prevent stenosis. This patent doesnot disclose the possibility of heating the stent by externalenergy-providing means, i.e. the possibility of heating the stent whenit is not physically connected to the catheter. Also, it does notdisclose the possibility of using materials which show magnetichysteresis for at least part of the stent. Thereby, it is not easy tocontrol the ablation temperature of the stent, in fact, the energydelivered to the stent should be monitored very closely as it depends ona multitude of factors, such as the electrical resistance of the stent,the amount and type of electrical current that is sent through thewires, the resistance of these wires, the quality of the thermal contactbetween stent and vessel wall.

Us patent application 2005/0027306 discloses a catheterization devicefor delivering a self-expanding stent. The device has an inner shaft andan outer shaft moveable with respect to the inner shaft. Theself-expanding stent is received on the inner shaft adjacent its distalend. A tapered tip is located on the inner shaft distal end and it formsa smooth transition from the delivery device to a guidewire extendingtherethrough. A handle allows a practitioner to deploy the stent singlehandedly. The stent may have its segments in a first radialconfiguration for delivery of the stent or the stent may have aplurality of segments in a first radial configuration and a plurality ofsecond segments in a second radial position.

US patent application 2005/0101946 discloses another method and systemfor treating AF by ablation of a pulmonary vein, using a stent which hasa resonant circuit. The stent can be implanted at the site of ablationand subsequently activated by external energy-providing means, inparticular by an electromagnetic field with the resonating frequency ofthe resonant circuit of the stent. The application does not disclose thepossibility of using materials which show magnetic hysteresis for atleast part of the stent, and to use the hysteresis effect for activatingthe stent. Thereby, it is also in this way not easy to control theablation temperature of the stent. The energy delivered to the stentshould be monitored very closely as it depends on a multitude of factorsand the temperature of the stent is not under control, such as theelectrical resistance of the stent and the resonant circuit of thestent, the magnitude of the RF field at the site of the stent, thequality of the thermal contact between stent and vessel wall.

European patent application EP 1 036 574 discloses a device and methodfor heating an implanted stent up to a certain temperature, usingexternal energy-providing means. The stent can be heated up through theeffect of magnetic hysteresis. However, in this patent application, thetemperature is controlled by an external controlling system whichmeasures the temperature of the stent via e.g. an infrared camera, andalters the energy provided with the external energy-providing meansaccordingly. Hereby, it is not explicitly disclosed that the system isused for ablation. Furthermore, the temperature is controlled by anexternal feedback system, and not e.g. by the material properties of thestent. Moreover, European patent application EP 1 036 574 does notdisclose that the stent or implant may subtend at least a substantiallycomplete circumferential band of the vessel's inner wall.

There remains a need in the art for improved devices, systems andmethods for the ablation of a substantially complete circumferentialband around a vessel's wall from the inside. The present invention aimsto resolve at least some of the problems mentioned above, e.g. to makesure that the ablation is performed for a substantially completecircumferential band around a vessel's wall from the inside, that theablation itself can be triggered with external means and this multipletimes if necessary, that the ablation temperature is well under controland does not depend on less-controlled elements in the treatment or onan intricate monitoring system, etc.

SUMMARY OF THE INVENTION

The present invention provides a system of one or more implant devicesand excitation device, an implant device and a method using the systemand one or more devices for the treatment of arterial and venousstructures. The present invention also concerns implant devices, asystem of implant devices and external excitation means, and a methodfor positioning one or more implant devices in a vessel, andsubsequently heating these implant devices, preferably simultaneously,thereby transferring heat from implant devices to the vessel's innerwall.

In a first aspect, the present invention provides a system for ablationof at least a part of a vessel's wall from the inside, comprised of

-   -   a self-expanding implant device, adapted to be implanted and        deployed within said vessel; whereby said implant comprises an        ablation region along at least a portion of its length, said        ablation region being adapted for surface contact with said        vessel and said ablation region subtending at least a        substantially complete circumferential band and being effective        to ablate a signal-blocking path within said vessel upon        application of energy to the implant;    -   external energy-providing means, which are spatially separated        from the implant device and able to provide energy to the        implant device for increasing the temperature of the ablation        region of the implant device up to an ablation temperature.

In a preferred embodiment, the system comprises more than one implantdevice, each of which adapted to be implanted and deployed within one ormore vessels.

These implant devices can each be adapted to be implanted and deployedwithin one or more pulmonary veins.

In a particular preferred embodiment, one or more implant devices of thesystem comprise a proximal portion having a first diameter and a distalportion having a second diameter that is less than the first diameterand that is sufficient to enable said implants to seat within one ormore vessels.

In a preferred embodiment, at least part of the one or more implantdevices of the system is made from at least one material which showsmagnetic hysteresis, such as a ferromagnetic, ferrimagnetic oranti-ferromagnetic material. Furthermore, the external energy-providingmeans may create a time-varying magnetic field at the position of theone or more implant devices. In a more preferred embodiment, thistime-varying magnetic field is created by an electric coil through whicha time-varying electrical current is sent.

In another embodiment, the system also comprises

-   -   a sheath suitable for transporting and delivering the one or        more implant devices to or near the desired position in the one        or more vessels;    -   a guidewire suitable for sequentially guiding the sheath with        the one or more implants to the desired position in the one or        more vessels.

In a second aspect, the present invention provides a self-expandingimplant device adapted to be implanted and deployed within a vessel;said implant comprising an ablation region along at least a portion ofits length, the ablation region being adapted for surface contact withthe vessel and the ablation region subtending at least a substantiallycomplete circumferential band and being effective to ablate asignal-blocking path within the vessel upon application of energy to theimplant; whereby said ablation region comprises at least one materialwhich shows magnetic hysteresis, such as a ferromagnetic, ferrimagneticor anti-ferromagnetic material.

In a similar aspect, the present invention provides a, preferablyself-expanding, implant device adapted to be implanted and deployedwithin a vessel, said implant comprising an ablation region along atleast a portion of its length, the ablation region being adapted forsurface contact with the vessel and for subtending at least asubstantially complete circumferential band or a spiraling band and saidablation region effective to ablate a signal-blocking path within thevessel upon application of energy to the implant device, wherebypreferably said ablation region comprises at least one material whichshows magnetic hysteresis, such as a ferromagnetic, ferrimagnetic oranti-ferromagnetic material.

In a preferred embodiment, the implant device is adapted to be implantedand deployed within a pulmonary vein. In a more preferred embodiment,said ablation region of said implant device is adapted for surfacecontact with said pulmonary veins and for subtending at least asubstantially complete circumferential band for ensuring PVI.

In a preferred embodiment, the implant device comprises a shape which isadapted for a renal artery. In a more preferred embodiment, saidablation region of said implant device is adapted for surface contactwith said renal arteries and for subtending at least a substantiallyspiraling band, e.g. for treating renal hypertension by ablation andconsequential blocking renal sympathetic nerve signals.

In a particular preferred embodiment, parts of the implant device aremade from more than one material showing magnetic hysteresis and whichhave different Curie or Néel temperatures.

In a more preferred embodiment the implant device is suitable forlong-term implantation. In another preferred embodiment, the implantdevice is a bio-resorbable implant device or an implant that disappears,e.g. by evaporation, after one or more ablations. Furthermore, theimplant device may comprise a proximal portion having a first diameterand a distal portion having a second diameter that is less than thefirst diameter and that is sufficient to enable said implant device toseat within a vessel. The implant device may further comprise anchoringmeans at or near the proximal or distal portion of said implant device,said anchoring means being suitable for keeping the device at or nearthe same position compared to the vessel's inner wall.

In a preferred embodiment, part of said implant device which can comeinto contact with the patient's blood when said implant device isimplanted, is thermally isolated from the rest of the implant devicesuch that the blood is not heated or overheated during the excitation ofthe implant device. Such part can comprise an adluminal coating or alayer with high isolation characteristics.

In a preferred embodiment, said implant comprises a thermoactive coatingcomprising an activation temperature between 35° C. and 37° C. so thatthe body temperature would trigger activation. In an alternativelypreferred embodiment, said implant comprises a thermoactive coatingcomprising an activation temperature above 45° C. so that activation istriggered only when said ablation region is heated by said externalenergy-providing means.

In a preferred embodiment, the implant device comprises a core region ofmaterial with a certain Curie temperature, surrounded by other materialwith thermal and/or elastic properties suitable for the implant device'spurpose.

In an embodiment, said implant comprises substances capable of producinga lesion of limited necrosis and/or neurotoxicity.

In a preferred embodiment, the implant device comprises cavities whichare filled with one or more substances and which open when the implantis heated. In a more preferred embodiment, these substances are mixedbefore being released into the patient's body or vessel wall, e.g. todeliver a two-component neurotixine. In another preferred embodiment,these substances are a selection or a composition of one or more of thefollowing substances:

-   -   ethanol;    -   tetrodotoxin and batrachotoxin;    -   maurotoxin, agitoxin, charybdotoxin, margatoxin, slotoxin,        scyllatoxin or hefutoxin;    -   calciseptine, taicatoxin, calcicludine, or PhTx3;    -   botulinum toxide;    -   cytochalasin D, rapamycin, sirolimus, zotarolimus, everolimus,        paclitaxel;    -   glutamate;    -   isoquinoline;    -   N-methyl-(R)-salsolinol;    -   Beta-carboline derivates.

In a further aspect, the present invention provides a system comprisingone, two, three, four or more implant devices, such as 5, 6, 7, 8, 9 or10 or more implant devices according to the present invention.Preferably this system comprises external energy-providing means, whichare spatially separated from said implant devices and able to provideenergy to said implant devices for increasing the temperature of theablation regions of the implant devices up to an ablation temperature,and/or a sheath suitable for transporting and delivering the one or moreimplant devices to or near the desired position in the one or morevessels, and/or a guidewire suitable for sequentially guiding the sheathwith the one or more implants to the desired position in the one or morevessels. In a preferred embodiment, the system comprises one, two, threeor four implant devices according to the present invention, each ofwhich adapted for a corresponding pulmonary vein and/or one or twoimplant devices according to the present invention, each of whichadapted for a corresponding renal artery.

In yet a further aspect, the present invention provides a method for thetreatment of a patient with atrial fibrillation by pulmonary veinisolation via ablation of a substantially complete circumferential bandon one or more pulmonary veins' walls from the inside, comprising thesteps of

-   -   implanting one or more implant devices in one or more pulmonary        veins by means of a sheath and a guidewire, said implant devices        each comprising an ablation region along at least a portion of        their length, said ablation regions being adapted for surface        contact with said pulmonary veins and said ablation regions        subtending at least a substantially complete circumferential        band and being effective to ablate a signal-blocking path within        said pulmonary veins upon application of energy to said implant        devices;    -   retracting the sheath and guidewire;    -   subsequently heating the ablation region of the one or more        implant devices by external energy-providing means, which are        spatially separated from the implant device.

In a similar aspect, the present invention provides a method for heatingone, two or more implant devices, which are suitable to be implanted inone, two or more vessels, comprising the steps of:

-   -   subsequently positioning said implant devices in said vessels by        means of a sheath and a guidewire, said implant devices each        comprising an ablation region along at least a portion of their        length, said ablation region subtending at least a substantially        complete circumferential band or a substantially spiraling band,        said implant devices effective for ablating a signal-blocking        path within said vessels upon application of energy to said        implant devices;    -   retracting the sheath and guidewire;    -   heating the ablation region of said implant devices by external        energy-providing means which are spatially separated from said        implant devices characterized in that said heating occurs after        said sheath and guidewire are retracted and said heating of said        implant devices occurs simultaneously.

In a preferred embodiment of the method, a recovery period is observedprior to heating the ablation region of the one or more implant devicesby external energy-providing means. Furthermore, this recovery periodmay be long enough to allow the one or more implant devices to beintegrated into the vessel wall or endothelialized.

In a particular preferred embodiment of the method, the step of heatingthe ablation region of the one or more implant devices by externalenergy-providing means, which are spatially separated from the implantdevice, is performed more than once, e.g. at well-spaced time-intervals,whenever it is deemed necessary, etc.

In a more preferred embodiment of the method, one or more implantdevices as described in this document are being used.

In a still more preferred embodiment of the method, use is made of asystem as described in this document.

DESCRIPTION OF FIGURES

FIGS. 1 to 5, and 9 to 11 schematically represent different embodimentsof an implant for the treatment of arterial and venous structuresaccording to the invention.

FIGS. 6 to 8 schematically represent a detail of a portion of an implantaccording to the invention.

FIG. 12 schematically represents an embodiment of a sheath withguidewire and implant device.

FIG. 13 schematically shows the way the catheterization can be done inorder to deliver one or more implants in the PVs.

FIG. 14 schematically represents an embodiment of the externalenergy-providing means as it can be used for treating a patient.

FIG. 15 schematically represents an embodiment of an implant in place ata PV.

FIG. 16 shows a magnetic hysteresis loop for a ferromagnet: H is theintensity of the magnetic field, M is the magnetic moment of the sample,H_(c) is the coercive field, M_(r) is the residual magnetic moment, andM_(s) is the saturation magnetic moment. The nonlimiting hysteresis loopis shown by the dotted line. The domain structure of the sample forcertain points on the loop is shown schematically.

FIG. 17 shows the typical temperature dependence of the hysteresis loopof a magnetic material with Curie or Néel temperature of 140° C.

FIG. 18 shows an embodiment of an implant which has an hour-glass shape,whereby near the middle region, where the diameter becomes smaller, aset of heating rings is attached around the hour-glass shaped part ofthe implant.

FIG. 19 shows an embodiment of an implant comprising a fuse, so that atcertain temperatures, the circuit that may be generated getsinterrupted. FIG. 19a shows a detailed view of the fuse.

In a different configuration, as shown in FIG. 20, the metal implant canbe build up of memory shape alloys. Details of the on and off positionof the switch or fuse are shown in FIGS. 20a and 20b respectively.

In a still different configuration as shown in FIG. 21 and a detail inFIG. 21a , the implant consists of two different materials.

An embodiment of the implant with an extensive coating formed around theimplant, but almost exclusively on the ADLUMINAL side is illustrated inFIG. 22.

DETAILED DESCRIPTION OF THE INVENTION

The present invention concerns a system of one or more implant devicesand excitation device, an implant device and a method using the systemand one or more devices for the treatment of arterial and venousstructures. The present invention also concerns implant devices, asystem of implant devices and external excitation means, and a methodfor positioning one or more implant devices in a vessel, andsubsequently heating these implant devices, preferably simultaneously,thereby transferring heat from implant devices to the vessel's innerwall.

Unless otherwise defined, all terms used in disclosing the invention,including technical and scientific terms, have the meaning as commonlyunderstood by one of ordinary skill in the art to which this inventionbelongs. By means of further guidance, term definitions are included tobetter appreciate the teaching of the present invention.

As used herein, the following terms have the following meanings:

“A”, “an”, and “the” as used herein refers to both singular and pluralreferents unless the context clearly dictates otherwise. By way ofexample, “a compartment” refers to one or more than one compartment.

“About” as used herein referring to a measurable value such as aparameter, an amount, a temporal duration, and the like, is meant toencompass variations of +/−20% or less, preferably +/−10% or less, morepreferably +/−5% or less, even more preferably +/−1% or less, and stillmore preferably +/−0.1% or less of and from the specified value, in sofar such variations are appropriate to perform in the disclosedinvention. However, it is to be understood that the value to which themodifier “about” refers is itself also specifically disclosed.

“Comprise,” “comprising,” and “comprises” and “comprised of” as usedherein are synonymous with “include”, “including”, “includes” or“contain”, “containing”, “contains” and are inclusive or open-endedterms that specifies the presence of what follows e.g. component and donot exclude or preclude the presence of additional, non-recitedcomponents, features, element, members, steps, known in the art ordisclosed therein.

The recitation of numerical ranges by endpoints includes all numbers andfractions subsumed within that range, as well as the recited endpoints.

The expression “% by weight” (weight percent), here and throughout thedescription unless otherwise defined, refers to the relative weight ofthe respective component based on the overall weight of the formulation.

The expressions “implant” and “implant device” are used interchangeablyin this application. An implant device as used in the present context,refers to an artificial tube or tube-like device, i.e. a device whichhas a circumferential wall and which is at least partly open at the topand at the bottom, whereby said circumferential wall may or may not haveopenings or holes, said tube or tube-like device intended to be placedinside a vessel of the body of a patient, e.g. a vein, or inside avessel of a human or animal corpse or model of a human or animal body.In the present context, the terms “implant” and “implant device” do notnecessarily mean that the device is placed inside a vessel to keep thisvessel open for fluids, although this can be one of the effects of thedevice. The implant device is, however, meant to be seated in a fixedposition compared to the vessel and not to move due to fluid flowthrough the vessel. When using the term “implanted” device, it is meantthat the implant or implant device has been implanted. In an embodiment,the implant device is a stent device, meaning that the device has theintended effect of keeping the vessel open for fluids when implanted.

The terms “catheter” and “sheath” are used interchangeably in thisapplication.

The term “guidewire” is used in this application for a device which canbe controllably guided when inserted into a body. In a preferredembodiment, it is a catheter, i.e. a guiding catheter. In anotherembodiment, it is solid and does not have a lumen.

The terms “Curie temperature” and “Néel temperature” refer to thetemperature above which ferromagnetic, anti-ferromagnetic andferrimagnetic materials become para- or diamagnetic, and are usedinterchangeably in the following.

In a first aspect, the present invention provides a system for ablationof at least a part of a vessel's wall from the inside, comprised of

-   -   a self-expanding implant device, adapted to be implanted and        deployed within said vessel; whereby said implant comprises an        ablation region along at least a portion of its length, said        ablation region being adapted for surface contact with said        vessel and said ablation region subtending at least a        substantially complete circumferential band and being effective        to ablate a signal-blocking path within said vessel upon        application of energy to the implant;    -   external energy-providing means, which are spatially separated        from the implant device and able to provide energy to the        implant device for increasing the temperature of the ablation        region of the implant device up to an ablation temperature.

The implant device is self-expanding, for example, being formed of ashape memory alloy, and is configured to lodge against the interior wallof e.g. a pulmonary vein. The implant may be formed as a loop, helix,progressively wound helix or other suitable shape. It may have anchoringmeans such as hooks or barbs near the ends, preferably near the proximalend at the side of the antrum or near the distal end at the side of theostium or deeper into the vessel when implanted in a PV near the leftatrium. The implant device may comprise an ablation region which is incontact with the ablation region of the vessel's wall. Preferably, theablation region comprises a substantially complete circumferential bandaround the vessel's wall. The ablation region may comprise a completecircumferential band around the vessel's inner wall, or the ablationregion may comprise a complete circumferential band around the vessel'swall and this for the complete thickness of the wall. With‘substantially’ is meant that the ablation region is such that allelectric signals arising at one side of the ablation region do not reachthe other side, i.e. a signal-blocking path is ablated. Energy can beprovided to the implant device by external means through electromagneticradiation, through hysteresis heating via a time-varying magnetic field,by direct and indirect induction and by Joule heating, by acoustic,mechanical-vibrational and chemical energy means, by a thermal/chemicalor mechanical/chemical release system.

One of the advantages of the present invention over prior arttechniques, is that the one or more implant devices can be heated upsimultaneously, i.e. the delivery of energy to the implants happens atthe same time and does not need to be done sequentially. This saves timeand increases the patient's comfort. Through built-in control of thetemperature, e.g. by using magnetic material with a specified Curietemperature or by using the proper insulation material in the implant,additional energy delivery will not further increase the temperaturebuilt-up in the implant.

By ‘external’ energy-providing means is meant that these means arespatially separated from the implant device, i.e. there is no physicalconnection between the energy-providing means and the implant device,or, more specifically, the energy-providing means are completely outsidethe patient's body and the patient's skin can remain intact while theenergy is provided.

The temperature of ablation region is specified according to the needsof the treatment. Depending on the ablation temperature needed, theimplant device can be engineered to be warmer at certain regions than inother regions by using the magnetic and thermal properties of thematerials of which the implant device is composed. In an embodiment,parts of the implant device may be thermally isolated from other partsof the implant device or from parts of the body or bodily fluids.

In a preferred embodiment, the system comprises more than one implantdevice, each of which adapted to be implanted and deployed within one ormore vessels. These implant devices can each be adapted to be implantedand deployed within one or more pulmonary veins.

In about 60% of the patients, four PVs debouch separately into the leftatrium. However, in other patients, two PVs have a common debouch and instill other patients, there can be a fifth vein debouching in the leftatrium. It should be clear that the one or more implant devices can beadapted to fit into all these veins, also for the less occurring cases.

In a particular preferred embodiment, one or more implant devices of thesystem comprise a proximal portion having a first diameter and a distalportion having a second diameter that is less than the first diameterand that is sufficient to enable said implants to seat within one ormore vessels.

Mainly for the right PVs, an implant as described above can be used,since these PVs usually have a different diameter in their ostium thanin their antrum.

In a particular preferred embodiment, one or more implant devices of thesystem comprise a proximal portion having a first diameter and a distalportion having a second diameter that is greater than or equal to thefirst diameter and that is sufficient to enable said implants to seatwithin one or more vessels.

Mainly for the left PVs, an implant as described above can be used,since these PVs usually have the same or a similar diameter in theirostium as in their antrum. In some cases the diameter in the distal partof the PV is larger than the diameter of the proximal part.

Obviously, the way a PV is connected to the left atrium depends on thepatient. The shape of antrum and ostium can be different for each PV andeach patient. However, it should be clear to the person skilled in theart that the proximal portion with the larger diameter is to be placednear the antrum, while the distal portion with the smaller diameter isplace near the ostium or deeper inside the PV. In case the implantdevice is implanted in another type of vessel, it should be clear thatthe shape of the implant device can be adapted so as to fit into thespecific vessel.

In order to make the shape and dimensions of the implants, it ispossible by a scanning technique such as CT-scan or MRI, to collect dataon the varying diameter of the vessel when going from the ostium to theantrum. From these data, one can derive the necessary shape anddimensions of the implants e.g. for all four PVs of a patient. Againthis measuring can be done without a surgical procedure, therebyincreasing the patient's comfort and wellbeing and reducing medicalrisks. After this measuring, the implants can be custom-made to fit thepatient's vessel or vessels.

In a preferred embodiment, at least part of the one or more implantdevices of the system is made from at least one material which showsmagnetic hysteresis, such as a ferromagnetic, ferrimagnetic oranti-ferromagnetic material. Furthermore, the external energy-providingmeans may create a time-varying magnetic field at the position of theone or more implant devices. In a more preferred embodiment, thistime-varying magnetic field is created by an electric coil through whicha time-varying electrical current is sent.

Magnetic hysteresis arises in a plethora of materials. Most known andmost used are the ferromagnetic, anti-ferromagnetic and ferrimagneticmaterials. These have highly non-linear magnetic properties, i.e. themagnetic induction field is not directly proportional to the appliedmagnetic field inside the material. However, all these material losetheir specific magnetic properties above a certain temperature, calledthe Curie or Néel temperature. This temperature is material-specific.Above this temperature, the ferromagnetic, anti-ferromagnetic andferrimagnetic materials become para- or diamagnetic and thereby losetheir non-linear magnetic properties. The non-linear magnetic propertiesof ferromagnetic, anti-ferromagnetic and ferrimagnetic materials can bededuced from the hysteresis that is observed when applying atime-varying magnetic field.

Magnetic hysteresis is observed in magnetic materials, such asferromagnets. The main feature of ferromagnets is the presence ofspontaneous magnetization. A ferromagnet usually is not uniformlymagnetized but is divided into domains—regions of uniform spontaneousmagnetization whose degree of magnetization (the magnetic moment perunit volume) is identical, although the directions are different. Underthe effect of an external magnetic field the number and size of thedomains magnetized along the field increase at the expense of otherdomains. Moreover, the magnetic moments of certain domains may rotate inthe direction of the field. As a result the magnetic moment of thesample increases.

The dependence of the magnetic moment M of a ferromagnetic sample on theintensity H of the external magnetic field (the magnetization curve) isshown in FIG. 16. In a sufficiently strong magnetic field the sample ismagnetized to saturation (as the field increases further, the value of Mremains virtually unchanged—point A). Here the sample consists of onedomain with a magnetic moment of saturation M_(s) oriented along thefield. As the intensity H of the external magnetic field is reduced, themagnetic moment M of the sample will decline along curve I primarilybecause of the appearance and growth of domains whose magnetic moment isoriented against the field. The growth of the domains is due to themovement of the domain walls. This movement is hindered by the presencein the sample of various defects (such as impurities or inhomogeneities)that strengthen the domain walls at some points; very strong magneticfields are required to displace them. Therefore as the field H drops tozero, the so-called residual magnetic moment M_(r) (point B) isretained. A sample can be completely demagnetized only in a sufficientlystrong field of opposite direction, which is called a coercive field(coercive force) H_(c) (point C). As the magnetic field of reverseorientation is further increased, the sample is once again magnetizedalong the field to saturation (point D). Magnetic reversal (from point Dto point A) takes place along curve II. Thus, as the field undergoes acyclical change, the curve characterizing the change in the magneticmoment of the sample forms a magnetic hysteresis loop. If the field Hchanges cyclically with such limits that magnetization does not reachsaturation, a nonlimiting magnetic hysteresis loop is produced (curveIII). By reducing the extent of the change in field H to zero, thesample can be completely demagnetized (point O can be reached). Themagnetization of the sample from point O proceeds along curve IV.

In magnetic hysteresis different values of the magnetic moment Mcorrespond to the same value of the external magnetic field intensity H.This nonuniqueness is due to the influence of the states of the samplethat precede the given state (that is, to the magnetic prehistory of thesample).

The shape and size of magnetic hysteresis loops and the quantity H_(c)may range within wide limits in various ferromagnets. For example, inpure iron, H_(c)=1 oersted, and in a magnico alloy H_(c)=580 oersteds. Amagnetic hysteresis loop is strongly affected by processing of thematerial, during which the number of defects is changed. The area of amagnetic hysteresis loop is equal to the energy lost in the sample inone cycle of field change. This energy is also proportional to the totalvolume of ferromagnetic material in the sample. This energy ultimatelyis used to heat the sample. Such energy losses are called hysteresislosses. In cases when losses to hysteresis are undesirable (for example,in transformer cores and in the stators and rotors of electricalmachinery), magnetically soft materials with a low H_(c) and a smallhysteresis loop area are used. On the other hand, magnetically hardmaterials with a high H_(c) are required to manufacture permanentmagnets.

As the frequency of the alternating magnetic field (the number ofmagnetic reversal cycles per unit time) increases, other losses causedby eddy currents and magnetic viscosity are added to hysteresis losses.At high frequencies the area of the hysteresis loop increasescorrespondingly. Such a loop is sometimes called a dynamic loop, incontrast to the static loop described above.

Many other properties of a ferromagnet, such as electrical resistanceand mechanical deformation, depend on the magnetic moment. A change inmagnetic moment also brings about a change in these properties—forexample, galvanomagnetic and magnetostrictive hysteresis, respectively,are observed.

The hysteresis loop depends on the temperature. FIG. 17 shows thetypical temperature dependence of the hysteresis loop of a magneticmaterial with Curie or Néel temperature of 140° C. Note that only thetemperature dependence of the shape is characteristic and no units aregiven on the axes, the figure is meant for illustration purposes. It isobserved that the hysteresis loop changes with temperature, becomingsharper and thinner, and eventually disappearing at the Curie or Néeltemperature. From this temperature onwards, the material becomes para-or diamagnetic and no heating losses due to hysteresis are observed.This means that the material does not heat up anymore, at least not dueto hysteresis effects, and remains at the Curie or Néel temperature. (Inthe following, the two terms ‘Curie’ and ‘Néel’ temperature can be usedinterchangeably.) It should be remarked that heating due to othereffects, such as direct or indirect induction may still be possible, butthese effects are negligible in the present case, especially whencompared to the gigantic heating capabilities by hysteresis effects.

It should be now clear to the skilled person that when the ablationregion of an implant device comprises material with Curie temperature ofe.g. 40° C., the implant will be heated up to this temperature and notmore when being subjected to a time-varying magnetic field, e.g. by theexternal energy-providing means of the system of the present invention.If the ablation temperature needs to be 42° C. or 45° C., the magneticmaterial used in the implant may be altered to have this temperature asCurie temperature. This can be done by e.g. changing the composition ofan alloy of magnetic material. The Curie temperature of a magneticmaterial can be very precisely engineered.

In a preferred embodiment, the magnetic materials used in the implantdevice are a combination or alloy of the following materials: MnAs, Gd,Gd with a thin Fe overlayer, Ni—Fe alloy with around 29.5 at.% Ni whichis cooled slowly from 1000° C., Ni—Fe with 30 at.% Ni, Cr, CoO, ZnFe₂O₄,are any magnetic material with Curie or Néel temperature above 10, 20,25, 30, 35, 40° C. and/or below 75, 70, 65, 60, 55, 50, 45, 40° C.

The Curie or Néel temperatures of alloys or composite materials candepend highly on the procedure for making these materials. Especiallyannealing procedures may be important. Also other ways of altering theCurie temperatures such as ion radiation can be used to provide thedesired material. One can use any magnetic material, alloy, binaryalloy, ternary alloy or quaternary alloy with the desired Curie or Néeltemperature as specified in standard reference works such as theLandolt-Börnstein database.

In another embodiment, the system also comprises

-   -   a sheath suitable for transporting and delivering the one or        more implant devices to or near the desired position in the one        or more vessels;    -   a guidewire suitable for sequentially guiding the sheath with        the one or

more implants to the desired position in the one or more vessels. Thesheath in this embodiment includes an implant delivery system capable ofdelivering the one or more implant devices as described in this text. Anembodiment of such sheath with delivery device and guidewire is shown inFIG. 12.

In a second aspect, the present invention provides a self-expandingimplant device adapted to be implanted and deployed within a vessel;said implant comprising an ablation region along at least a portion ofits length, the ablation region being adapted for surface contact withthe vessel and the ablation region subtending at least a substantiallycomplete circumferential band and being effective to ablate asignal-blocking path within the vessel upon application of energy to theimplant; whereby said ablation region comprises at least one materialwhich shows magnetic hysteresis, such as a ferromagnetic, ferrimagneticor anti-ferromagnetic material.

Preferably said material comprises a ferrous fluid, i.e. ferromagnetic,ferrimagnetic and/or anti-ferromagnetic particles suspended in a heatconducting fluidum, whereby said material is preferably contained withinsaid implant device. In a more preferred embodiment, said implant devicecomprises one or more fluid-tight cavities comprising saidferromagnetic, ferrimagnetic and/or anti-ferromagnetic particles in saidheat conducting fluidum. In an even more preferred embodiment, saidparticles comprise any or any combination of the following materials:SrFe₁₂O₁₉, Me_(a)—2W, Me_(a)—2Y, and Me_(a)—2Z, wherein 2W is BaO:2Me_(a)O:8 Fe₂O₃, 2Y is 2 (BaO:Me_(a)O:3 Fe₂O₃), and 2Z is 3 BaO:2Me_(a)O:12 Fe₂O₃, and wherein Me_(a) is a divalent cation, whereby thedivalent cation is preferably selected from Mg, Co, Mn and Zn, and/or 1Me_(b)O:1 Fe₂O₃, where Me_(b)O is a transition metal oxide selected fromNi, Co, Mn, and Zn, and/or metal alloys such as La_(0.8)Sr_(0.2)MnO₃,Y₃Fe_(5-x)M_(x)O₁₂ where M is Al, or Gd and 0<x<2, and/or metal alloysof any combination of Pd, Co, Ni, Fe, Cu, Al, and Si and/or metal alloysof any combination of Gd, Th, Dy, Ho, Er, and Tm with any combination ofNi, Co, and Fe and/or metal alloys RMn₂X where R is a rare earth, suchas La, Ce, Pr, or Nb and X is either Ge or Si. Particularly preferred isany or any combination of the following alloys: NiCu with 28% or 29.6%Ni, NiPd, PdCo with 6.15% Pd, NiSi with 4% Ni, (Ni,ZnO)Fe₂O₃,La_(0.8)Sr_(0.2)MnO_(x), Y₃Fe_(5-x)Al_(x)O12 with 1.0×1.7. The particlescan be of any size, preferably longer than 10 nanometers, morepreferably longer than 20 nanometers in the longest dimension, andsmaller than 500 micrometers, preferably smaller than 100 micrometers inthe longest dimension. In certain embodiments, said particles aresmaller than 1 micrometer, preferably smaller than 200 nanometers in thelongest dimension. In other embodiments, said particles are longer than1 micrometer, preferably longer than 20 micrometer in the longestdimension. Preferably said fluidum in which said particles are suspendedcomprises optimal heat conduction properties. In a preferred embodiment,said fluidum comprises a large heat capacity. In another preferredembodiment, said fluidum comprises a low heat capacity. The exactnature, amount and combination of which magnetic materials to use forthe particles and which fluidum to use, depends on the desiredtemperature and heat for e.g. inducing complete circumferential ablationof the inner wall of a pulmonary vein. In a preferred embodiment, saidmagnetic materials comprise a Curie or Néel temperature of 37, 38, 39,40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55° C. orany value in between or any combination thereof, preferably said Curieor Néel temperature is smaller than 75° C., more preferably smaller than70° C., even more preferably smaller than 65° C., yet more preferablysmaller than 62° C., still more preferably smaller than 59° C., yet evenmore preferably smaller than 57° C., still even more preferably smallerthan 55° C.

In a preferred embodiment, the implant device is adapted to be implantedand deployed within a pulmonary vein or a renal artery.

In a particular preferred embodiment, parts of the implant device aremade from more than one material showing magnetic hysteresis and whichhave different Curie or Néel temperatures.

Different temperatures cause different lesions on different placesdepending on which ablation regions of the implant device compriseswhich material. By thermally isolating parts of the implant device whichconsist of material with different Curie temperatures, a gradation inablation temperature along the implant device is possible. Also, partscomprising material with higher heat capacities will heat up moreslowly, but will remain hot longer afterwards, etc. Engineering ofablation characteristics can be done by engineering the implant makinguse of the magnetic and thermal properties of the materials used in theimplant.

In a more preferred embodiment the implant device is suitable forlong-term implantation. In another embodiment, the implant device is abio-resorbable implant device or an implant that disappears, e.g. byevaporation, after one or more ablation procedures. In a preferredembodiment, the implant device may comprise a proximal portion having afirst diameter and a distal portion having a second diameter that isless than the first diameter and that is sufficient to enable saidimplant device to seat within a vessel. The implant device may furthercomprise anchoring means at or near the proximal or distal portion ofsaid implant device, said anchoring means being suitable for keeping thedevice at or near the same position compared to the vessel's inner wall.The anchoring means may comprise hooks or barbs or anything else knownin the art for keeping an implant device at the desired position.

In a preferred embodiment, the implant device comprises an elasticallycompressible body comprising externally triggerable portions andprovided of anchoring means. The body may be mainly made of wires andmay, in expanded or released position, be provided of a narrowingtubular shape and/or a somewhat flattened narrowing tubular shape, i.e.that the cross sections at most positions along the longitudinal axisare oval shaped or the like, suitable to be placed inside the antrum ofa pulmonary vein. The body may also comprise between two and fivecircular wires, a first bigger circular or oval wire, and furthercircular or oval wires with decreasing diameter, positioned andmaintained at a distance from each other, at least when the body is in areleased or not compressed position. The body may be built up out ofbraided metal wires (that have multiple interconnections, crossingsand/or layers which allows for numerous connections with the vascularwall in the heart, more specifically in the atria, more specifically inthe left and right atrium, more specifically in the antrum or ostium ofthe pulmonary veins. The body may be conceived as a spirally shaped wireof which the diameter gradually goes down along its longitudinal axis.The windings of the implant device may be mutually connected withbridging upstanding wire portions providing closed loops to ensure fulland circular coverage of for example the antrum/ostium of the pulmonaryveins once the device is released. The body may show longitudinal metalbeads that are outward bending, and that still show severalinterconnections between them, to ultimately form a metal cage. Theimplant device may be characterized in that the greatest distancebetween two points that can be measured on the circular or oval wires ofthe body will range from 3 to 30 mm, more specifically from 5 mm to 20mm, even more specifically from 9 mm to 13 mm, if to be implanted at theostia of the pulmonary vein. The implant device may be characterized inthat the greatest distance between two points that can be measured onthe circular or oval wires of the body of the implant device will rangefrom 5 to 50 mm, more specifically from 8 mm to 40 mm, even morespecifically from 10 mm to 30 mm, if to be implanted at the site of theantrum. The body of the implant device may be mainly made of one or moremetal alloys. The body of the implant device may comprise portions whichare externally triggerable by means of an energy field or a combinationof energy fields chosen from electromagnetic radiation, direct orindirect induction, acoustic energy, mechanical vibration, heatingand/or changing other characteristics of the implant or portionsthereof. Some of the material used in the implant device may be of thetype that reacts, for example heats, in response to a remote appliedalternating magnetic field. Energy can be provided to the implant deviceby external means through electromagnetic radiation, through hysteresisheating via a time-varying magnetic field, by direct and indirectinduction and by Joule heating, by acoustic, mechanical-vibrational andchemical energy means, by a thermal/chemical or mechanical/chemicalrelease system. The body may comprise portions made of different metalalloys with optionally different ferromagnetic properties and/orabsorption coefficients, with specific response to alternating magneticfields. Portions of the body of the implant device may be provided ofone or more coatings with varying properties. The wire or wires or otherportions of the body of the implant device is/are composed of differentlayers made of different alloys and/or of other materials. The implantdevice may be further characterized in that different coatings or layersrepresent different responses to externally applied energy fields, forexample to externally applied alternating magnetic fields. An adluminalcoating or layer with high isolation characteristics may be provided tothe implant device. The body of the implant device may haveself-expanding properties thanks to the elastic characteristics of thematerial used, and thanks to the geometry of the body, and furtherexpansion is stopped when it encounters a counter pressure of about 10to 40, preferably 20 to 30, more preferably 22 to 28, even morepreferably around 25 mm Hg, equal to the distension pressure needed toalter the left atrium's anatomy. The implant device may be characterizedin that it is provided of toxic substances that are only released uponintroduction into the pulmonary vein/antrum, for example after applyingan external energy field, which toxic substances then produce a lesionof limited necrosis/neurotoxicity. These toxins may include, but are notlimited to ethanol, tetrodotoxin and batrachotoxin, maurotoxin,agitoxin, charybdotoxin, margatoxin, slotoxin, scyllatoxin andhefutoxin, calciseptine, taicatoxin, calcicludine, and PhTx3, botulinumtoxine, cytochalasin D, rapamycin, sirolimus, zotarolimus, everolimus,paclitaxel, glutamate, isoquinoline, N-methyl-(R)-salsolinol,Beta-carboline derivates. The implant device may be provided of micropores wherein substances are provided, which can be released by atriggering energy field. The implant device may be provided of athermoactive coating which is only activated upon temperatures above 35°C. so that the body temperature would trigger activation. The implantdevice may be provided of a thermoactive coating which is only activatedupon temperatures above 45° C. so that an external application of anenergy field would trigger activation. The implant device may beprovided of anchoring means which mainly consist of the elongated shapeand/or the expanding forces optionally in combination with the wiredstructure allowing partial insertion or impression in the wall of theheart, more specifically of the atria, more specifically of the left andright atrium, more specifically of the antrum or ostium of the pulmonaryveins. These anchoring means may also comprise hooks or barbs or thelike, optionally provided on the outwardly directed portions of theimplant.

In a preferred embodiment, said implant device comprises cavities whichare filled with one or more substances and which open when the implantis heated and/or which open when the implant acquires body temperature,and/or whereby said implant comprises a coating comprising one or moresubstances.

In a preferred embodiment, an implant device according to the presentinvention comprises a maximal circumference and a minimal circumferenceand a ratio between maximal and minimal circumference, whereby saidratio is smaller than 10, preferably smaller than 9, more preferablysmaller than 8, even more preferably smaller than 7, yet more preferablysmaller than 6 and larger than 1.1, preferably larger than 1.5, morepreferably larger than 2, even more preferably larger than 2.5, yet morepreferably larger than 3. In a preferred embodiment, the implant devicecomprises a variable circumference along a longitudinal direction of theimplant, said circumference varying between at least 20 mm, preferablyat least 25 mm, more preferably at least 30 mm, even more preferably atleast 36 mm, yet more preferably at least 42 mm, still more preferablyat least 48 mm and at most 375 mm, more preferably at most 350 mm, evenmore preferably at most 325 mm, yet more preferably at most 300 mm,still even more preferably at most 275 mm, yet even more preferably atmost 250 mm. Such a ratio or dimension may be necessary to ensure thatan essentially circumferential band of the vessel's inner wall would besubtended, in particular in or near the antrum of said vessel, inparticular if the vessel is a pulmonary vein.

In a particularly preferred embodiment, said circumference may be atmost 200%, preferably at most 190%, more preferably at most 180%, evenmore preferably at most 170%, yet more preferably at most 160%, stillmore preferably at most 150% of the original diameter of the vessel forwhich the implant device is adapted, e.g. of the pulmonary vein or ofthe antrum of the pulmonary vein, or of the renal artery, etc. when theself-expanded implant device is in an expanded state.

In a preferred embodiment, the implant device comprises an outer surfacecompri.sing zig-zag or woven or braided material, drawn tubes,eccentrically drawn tubes, hollow struts, hollow struts filled withfluid, or any combination thereof.

In a preferred embodiment, an implant device according to the presentinvention comprises an essentially cylindrical shape preferablycomprising a diameter which is at least 2 mm, preferably at least 3 mm,more preferably at least 4 mm, even more preferably at least 5 mm, yetmore preferably at least 6 mm and at most 20 mm, preferably at most 16mm, more preferably at most 13 mm, even more preferably at most 10 mm,yet more preferably at most 9 mm. Such a shape or dimension may benecessary to ensure that a circumferential or spiraling band of thevessel's inner wall would be subtended, in particular in an essentiallycylindrical portion of said vessel, in particular if the vessel is arenal artery.

In a preferred embodiment, an implant device according to the presentinvention comprises a distal portion and a proximal portion, wherebysaid ablation region is located within 50%, preferably within 40%, morepreferably within 30% of the implant's total length from the proximalportion. In a preferred embodiment, an implant device according to thepresent invention comprises a distal portion and a proximal portion,whereby said ablation region is located within 25 mm, preferably within20 mm, more preferably within 15 mm from the proximal portion. If theimplant device is positioned in a pulmonary vein for e.g. PVI, theproximal portion is intended to be positioned near the antrum, while thedistal portion is intended to be positioned towards the ostium. Locatingthe ablation region of the implant device closer to the proximal portionthus is more efficient to obtain a circumferential ablation in theantrum of the PV.

In a preferred embodiment, the implant device comprises a distal portionand a proximal portion, and comprising an anchoring device connected tothe ablation region of said implant via a thermally insulatingconnection for preventing overheating of said anchoring device,preferably whereby said anchoring device is connected to the distalportion. The anchoring device may comprise different material than therest of the implant device. In particular, the anchoring device may havedifferent thermal characteristics due to its dimensions, shape ormaterial. The anchoring device may be connected to the distal portion ofthe implant device in order to have optimal anchoring in e.g. the ostiumof a PV. The thermally insulating connection may comprise thermallyinsulating material, or its shape and dimensions may increase thermalinsulation, e.g. a number of thin straps or wires attaching theanchoring device to the ablation region.

In a preferred embodiment, the system for the treatment of arterial andvenous structures, comprises an implant device according to any of theabove embodiments and an excitation or energy-providing devicepreferably conceived to be used from the exterior of the patient, afterbeing provided of an implant device, whereby the excitation serves tochange the characteristics of the implant device in order to treat thearterial or venous structure where the implant device is located. Theexcitation device for the treatment of arterial and venous structures,may be conceived to be used in cooperation with an implant deviceaccording to any embodiment described in this text.

In a preferred embodiment the part of the implant device which can comeinto contact with the patient's blood when said implant device isimplanted, is thermally isolated from the rest of the implant devicesuch that the blood is not heated or overheated during the excitation ofthe implant device. Such part may comprise an adluminal coating or alayer with high isolation characteristics. It is clear that heating ofthe blood should be avoided as much as possible for the benefit andcomfort of a patient.

In another embodiment, the implant device comprises a core region ofmaterial with a certain Curie temperature, surrounded by other materialwith thermal and/or elastic properties suitable for the implant device'spurpose. As such, one can engineer the temperature profile through theimplant device. It should be clear that the parts of the implant whichare meant to contact the vessel wall and the form lesions by ablation,should be heated mostly while other parts of the implant, which are incontact with the vessel or the blood and are not meant to form lesions,should receive as little heat as possible for the wellbeing of apatient.

In still another embodiment, the implant device comprises cavities whichare filled with one or more substances and which open when the implantis heated. In a preferred embodiment, these substances are mixed beforebeing released into the patient's body or vessel wall, e.g. to deliver atwo-component neurotixine. In a more preferred embodiment, thesesubstances are a selection or a composition of one or more of thefollowing substances:

-   -   ethanol;    -   tetrodotoxin and batrachotoxin;    -   maurotoxin, agitoxin, charybdotoxin, margatoxin, slotoxin,        scyllatoxin or hefutoxin;    -   calciseptine, taicatoxin, calcicludine, or PhTx3;    -   botulinum toxide;    -   cytochalasin D, rapamycin, sirolimus, zotarolimus, everolimus,        paclitaxel;    -   glutamate;    -   isoquinoline;    -   N-methyl-(R)-salsolinol;    -   Beta-carboline derivates.

With such implants, it becomes possible to release the desiredsubstances into the vessel wall or the blood stream at the desiredmoment, by heating the implant with e.g. external energy providingmeans. Furthermore, the implant and cavities in the implant may bedesigned such that the two components of e.g. a two-componentneurotixine, are mixed before being released into the body.

In a preferred embodiment, an implant device according to the presentinvention comprises one or more deposits of toxin, preferably on anouter surface of said device, said deposits covered by a metal layercapable of being resolved by heating, preferably hysteresis heating.

In a further aspect, the present invention provides a method for thetreatment of a patient with atrial fibrillation by pulmonary veinisolation via ablation of a substantially complete circumferential bandon one or more pulmonary veins' inner walls, comprising the steps of

-   -   implanting one or more implant devices in one or more pulmonary        veins by means of a sheath and a guidewire, said implant devices        each comprising an ablation region along at least a portion of        their length, said ablation regions being adapted for surface        contact with said pulmonary veins and said ablation regions        subtending at least a substantially complete circumferential        band and being effective to ablate a signal-blocking path within        said pulmonary veins upon application of energy to said implant        devices;    -   retracting the sheath and guidewire;    -   subsequently heating the ablation region of the one or more        implant devices by external energy-providing means, which are        spatially separated from the implant device.

It should be stressed that in the above method, the heating of theimplant device occurs after the surgical procedure. This improves theease of the heating procedure and the comfort of the patient.

In a similar aspect, the present invention provides a method for heatingone, two or more implant devices, which are suitable to be implanted inone, two or more vessels, comprising the steps of:

-   -   subsequently positioning said implant devices in said vessels by        means of a sheath and a guidewire, said implant devices each        comprising an ablation region along at least a portion of their        length, said ablation region subtending at least a substantially        complete circumferential band or a substantially spiraling band,        said implant devices effective for ablating a signal-blocking        path within said vessels upon application of energy to said        implant devices;    -   retracting the sheath and guidewire;    -   heating the ablation region of said implant devices by external        energy-providing means which are spatially separated from said        implant devices characterized in that said heating occurs after        said sheath and guidewire are retracted and said heating of said        implant devices occurs simultaneously.

In a preferred embodiment of the method, a recovery period is observedprior to heating the ablation region of the one or more implant devicesby external energy-providing means. Furthermore, this recovery period islong enough to allow the one or more implant devices to be overgrown bybodily tissue. This recovery period may also be long enough to test ifthe implant devices are well positioned and do not move substantiallywithin the vessel.

The advantages of observing a waiting period are multiple: the patienthas time to recover from the surgical procedure, extra tests can beperformed during the waiting period to check whether the implant devicewas well implanted, bodily tissue can overgrow the implant device,thereby improving the contact of implant device with the vessel's innerwall and thus improving the efficiency of the ablation procedure, etc.

In a particular preferred embodiment of the method, the step of heatingthe ablation region of the one or more implant devices by externalenergy-providing means, which are spatially separated from the implantdevice, is performed repeatedly at well-spaced time-intervals.

The presented method has the main advantage that in case multipleablation procedures are necessary, no second surgical procedure isneeded, i.e. the implanted implant device or devices can be reused for asecond, third, . . . ablation procedure.

In a more preferred embodiment of the method, one or more implantdevices as described in this document are being used. Thereby theimplant devices can be engineered in order to produce the requiredeffects by engineering their shape, size, material composition, magneticand thermal properties, etc.

In a still more preferred embodiment of the method, use is made of asystem as described in this document. In this case, the implant devicecan be heated by the external energy-providing means and ahighly-controlled temperature of the ablation region of implant can bereached.

In a preferred embodiment, at least one implant device comprises a shapewhich is adapted for a pulmonary vein.

In a preferred embodiment, the vessels comprise one or more pulmonaryveins and said ablation regions of said implant devices are adapted forsurface contact with said pulmonary veins and subtending at least asubstantially complete circumferential band for ablating asignal-blocking path within said pulmonary veins upon application ofenergy to said implant devices. In a more preferred embodiment, theimplant devices are positioned at or near the antrums of the pulmonaryveins and/or the ablation regions of the implant devices are positionedsuch that they subtend essentially circumferential paths at or near theantrums of the pulmonary veins.

In a preferred embodiment, at least one implant device comprises a shapewhich is adapted for a renal artery.

In a preferred embodiment, said vessels comprise one or more renalarteries and said ablation regions of said implant devices being adaptedfor surface contact with said renal arteries and subtending at least asubstantially spiraling band for ablating a signal-blocking path withinsaid renal arteries upon application of energy to said implant devices.

In an embodiment of the method, the patient's vessels into which animplant is to be implanted are scanned using a 3D scanning techniquesuch as CT or MRI to collect data on the varying diameter of the vessele.g. when going from the ostium to the antrum. From these data, one canderive the necessary shape and dimensions of the implants e.g. for allfour PVs of a patient. This measuring can be done without a surgicalprocedure, thereby increasing the patient's comfort and wellbeing andreducing medical risks. After this measuring, the implants can becustom-made to fit the patient's vessel or vessels. Obviously,custom-made implants, in contrast with standard-sized implants, increasethe success rate of any medical procedure.

The following test describes the system, device and method according toembodiments of the present invention as they are applied to and testedin the treatment of pigs.

Twelve pigs were anaesthetized following good animal practices. Aftercatheterizing the right atrium, and following successful transseptalpuncture, a guiding catheter is placed in the left atrium. In an orderfree to choice by the cardiologist, the four pulmonary veins areconsecutively engaged by the guiding catheter. Following this, a 0.014″guidewire is put distally into the pulmonary vein of choice. Apreselected (guided by preprocedural CT scan) implant device is thenpositioned into the antrum/ostium of the pulmonary vein. Uponcontrolling the exact position—using the five radioopaque markers on theimplant device—the self-expanding implant device is then released intothe antrum/ostium/pulmonary vein so as to have the four most proximalmarkers outside of the pulmonary vein, and only have the fifth mostdistal marker residing inside the pulmonary vein. This procedure isrepeated for the four different pulmonary vein ostia, so that at the endof the procedure all four implants are in situ. The procedure is thanterminated, all catheters are withdrawn, hemostasis is achieved, and theanimals are awakened.

An average of two weeks later (14+/−5 days) the animals are placedinside the dedicated magnetic field generator, using the predefinedprotocol to activate the implant devices.

The day after the implant activation, the animals are recatheterized,again with placing a guiding catheter transseptally into the leftatrium. Electrophysiology catheters are the placed inside the leftatrium so that signal mapping can be performed. A lasso catheter isplaced inside the pulmonary veins so that after stimulation completeentrance block is proved. Consequently, exit pacing is performed,proving no atrial capture from the pulmonary veins (showing exit block),so that finally (bidirectional) complete isolation is confirmed.

All procedures are successful, with complete isolation shown in 47/48pulmonary veins (98%). No side effects or complications are noted.

Anatomopathology shows good apposition in 46/48 cases. Transmurallesions are present in 43/48 (96%) cases.

The following describes another test of the system, device and methodaccording to embodiments of the present invention in the treatment ofswine.

Twenty domestic swine will be utilized, aged approximately 6 months andweighing about 75 kilograms (165 pounds). All animals will receiveacetylsalicylic acid 325 mg and a loading dose of clopidogrel 600 mg onthe day of the procedure. An MRI of the brain is made before theprocedure.

Anesthesia will be induced with ketamine 33 mg/kg and midazolam 0.5mg/kg supplemented with a 5-mg/kg ketamine bolus and a 0.25-mg/kgmidazolam bolus for intubation. Following intubation, anesthesia will bemaintained with isoflurane 1-3% and fentanyl 30-100 mcg/kg/h. Femoralarterial access will be obtained percutaneously for hemodynamicmonitoring. Lidocaine 2-4 mg/kg intravenous (IV) bolus followed by 50mcg/kg/min continuous IV infusion will be administered for prophylactictreatment for arrhythmias. Vital sign and ECG monitoring is performedcontinuously.

Bilateral femoral venous access will be achieved percutaneously, and two9-Fr 80-cm sheaths will be positioned in the heart under fluoroscopicguidance. IV heparin will be administered to achieve an activatedclotting time >250 s. An 8.5-Fr intracardiac echo (ICE) catheter will beintroduced to visualize anatomy and facilitate transseptal puncture.Double transseptal puncture will be performed, and the ICE catheter isplaced in the LA. A 14-Fr deflectable guide sheath will be introducedover an exchange wire through one of the 9-Fr sheaths. The guide sheathwill be advanced into each separate pulmonary vein (PV) sequentially.Angiograms of the different PV will be acquired through contrastinjection (if necessary using a 6F catheter). Subsequently PVelectrograms will be recorded with a multipolar circular electrodecatheter.

Using the PV angiograms as a guidance, the most appropriate size ofimplant will be selected. Ideally two devices are implanted in eachswine. Device size is selected as to exceed the natural diameter of thePV by 15-20%. The deflectable guide sheath is aimed at the ostium of theselected PV and a new angiogram is made of the targeted vein. A secondspecially designed deflectable 13-Fr sheath loaded with the device and aJ-tip hydrophilic 0.016″ radio-opaque guide wire is prepared outside thebody of the swine. The device is thoroughly flushed to make sure no airis left inside the lumen of the sheath or inside the device. Afterhaving verified no air is left inside the lumen, the 13Fr sheath, deviceand guidewire are introduced through the aforementioned sheath. The 13Frsheath is connected to a pressurized saline infusion and to a contrastinjection system. The guidewire is advanced deep into the selected PV. Anew angiogram of the PV is made by injecting contrast though the sheathwith the device. The sheath with the device are advanced into the PV asfar as the length of the selected device. Another angiogram is made inorder to verify the optimal position of the device. Now the device isslowly released into the lumen of the PV by pulling back the 13Frsheath. At the final moment before definitively releasing the device,the position is checked by an angiography and by push-and-pull on thedevice itself that is already partially in place. Only after havingverified that the device is in the optimal position, the release systemof the device is activated, the device fully deploys into the vein andthe 13Fr sheath is pulled back and removed from the body after havingmade one final angiogram.

After having implanted the desired number of devices, the magnet isinstalled making sure the swine heart is in the target zone. Aspecifically designed thermometer is placed adjacent to the devicethrough the 14Fr sheath. The magnet is activated using the predefinedsettings (Amplitude, Frequency, Duration). The ICE catheter continuouslymonitors the production of micro-bubbles in the left atrium.

After completion of vein ablation, the multipolar circular electrodecatheter is returned to the veins and PV electrograms will again berecorded and compared to the original electrograms before ablation. Exitpacing from the circular electrode catheter is performed to provebidirectional block. New angiograms will be acquired at this stage.

Catheters will be removed and ten acute animals will be sacrificed withan overdose of barbiturates. Ten chronic animals will be recovered andgiven aspirin 325 mg and clopidogrel 75 mg daily and will be sacrificed30 days post procedure. A postmortem median sternotomy will beperformed, and the lungs and heart will be removed from the chest. Thelungs will be carefully dissected free from the heart, with effort tokeep the PVs intact. The LA will be opened along the roof and grosslyinspected. A tissue block containing each PV will be dissected from theLA. The veins containing the devices will be then sectionedcircumferentially for histopathological examination. The PV tissueblocks will be fixed in formalin and then stained with hematoxylin andeosin, Movat's pentachrome, and Masson's trichrome stains.

The invention is further described by the following non-limitingexamples which further illustrate the invention, and are not intendedto, nor should they be interpreted to, limit the scope of the invention.

EXAMPLES

FIG. 1 represents a preferred embodiment of an implant 1 according tothe present invention with circular cross-section (FIG. 1B) and ellipticcross-section (FIG. 1C). It should be clear that in the other figuresshowing embodiments of implants, the cross-sections can also be circularor elliptical, or basically any other shape which fits the vessel intowhich it is to be implanted best.

The represented implant 1 comprises a body 2, in this case shaped asnarrowing tubular cage and made of metal wires 3 or the like, suitableto be placed inside the antrum of a pulmonary vein.

More in particular, the body 2 is provided of in this case threecircular wires, a first bigger circular wire 4, an intermediatemid-sized second circular wire 5, and a third smaller circular wire 6.

The outlook of the body 2 may though be provided of more or less thanthree rings, for example two to five, more specifically three to four,or even more than five rings.

The first bigger circular wire 4 is connected with the intermediatemid-sized second circular wire 5 by means of in this case three straightinclined but upstanding wire portions 7.

In a similar manner, the intermediate mid-sized second circular wire 5is connected with the third smaller circular wire 6 by means of in thiscase also three straight inclined but upstanding wire portions 8.

The wire portions 8 are here located at intermediate positions withrespect to the wire portions 7.

The result is a narrowing tubular cage, which could also be described asa mainly conical or funnel shaped body 2, provided of three circularwires positioned at a distance from each other, at least when the body 2is in a released or not compressed position.

In general terms, the self-expanding body 2 is preferably provided of ashape that fits the anatomy of the vein, for example a pulmonary vein.

The circular wires may, according to a preferential embodiment, beprovided of a mainly oval shape such that the body 2 is built up ofdifferent oval rings of converging diameter, ideally adapted to theanatomy of the pulmonary veins.

These rings of the body 2 will typically range in diameter from 3 to 30mm, more specifically between 5 mm and 20 mm, even more specificallybetween 9 mm and 13 mm if to be implanted in the heart, morespecifically in the atria, more specifically in the left and rightatrium, more specifically in the antrum or ostium of the pulmonaryveins.

These rings of the body 2 will typically range from 5 mm to 50 mm, morespecifically from 8 mm to 40 mm, even more specifically between 10 mmand 30 mm if to be implanted at the site of the antrum.

The body 2 has self-expanding properties thanks to the elasticcharacteristics of the material used, and thanks to the geometry of thebody 2.

If a metal is used, it may be nitinol-based known for its superiorself-expansion properties.

The self-expanding body 2 is conceived to stop expanding when itencounters a pressure of about 1 to 150 mm Hg, more specifically 3 to 80mm Hg, more specifically 5 to 60 mm Hg, more specifically 10 to 40 mmHg, equal to the distension pressure needed to alter the left atrium'sanatomy.

Alternatively, a self-expanding cage may be conceived existing ofdifferent circular or oval shape rings that are interconnected. Therings may be formed so that a spiral form is created. The differentrings of the spiral will also be interconnected so that upon heating orupon release of substances from the cage, no openings for recurrence ofelectrical signals are left open.

In this case, the material used is of the type that reacts, for exampleheats, in response to a remote applied alternating magnetic field.

The principle of hysteresis causes the metal of the cage to heat up,depending on the absorptive properties of the metal alloy that builds upthe body 2.

Alternative is an electromagnetic field generator that changes polarityand therefore induces hysteresis heating in materials put inside thefield. The system may use the Curie temperatures (the temperature towhich a certain material can be heated, upon which further energydelivery does no longer change the temperature) that certain materialspossess, as to the target temperature that should and can be reached.For example, ZnFe₂O₄ is a material that has a Curie temperature between30 and 45 degrees Celsius.

A metal alloy cage that comprises ZnFe₂O₄ in its structure may thereforebe heated to exactly 45 degrees, close to the target temperaturedesirable for appropriate ablation purposes.

Another alternative to deliver energy to the cage could be directinduction, using a magnetic core, again making use of hysteresis heatingbut in a more directive way.

Another alternative to deliver energy to the cage could be to useelectromagnetic radiation through a thermical chemical-release systemwith external trigger, where the chemical is only released on demand andat the appropriate sites.

It is clear that still alternative energy field can be applied, such aselectromagnetic radiation, hysteresis heating, reaching Curietemperature, direct induction, thermal/chemical release system,mechanical/chemical release system, indirect induction, Joule heating,acoustic energy, mechanical vibration, chemical release system.

Alternatively, the body 2 can be provided of toxic substances that areonly released upon introduction into the pulmonary vein/antrum, forexample after applying an external energy field, which toxic substancesthen produce a lesion of limited necrosis/neurotoxicity.

In FIG. 2, an alternative embodiment of the implant 1 according to theinvention is represented.

The body is built up out of braided metal wires 9 that have multipleinterconnections, crossings and layers. This iteration allows fornumerous connections with the atrial vascular or other wall.

In FIG. 3, the implant 1 is conceived as a spirally shaped wire 10 ofwhich the diameter gradually goes down along its longitudinal axis.

The windings 10A-10D, in this case four, are mutually connected withbridging upstanding wire portions 8.

This embodiment thus differs from the embodiment as represented in FIG.1 by the single or continuous spirally shaped wire instead of thedifferent circular wires 4-6.

The bridging upstanding wire portions 8, apart from giving structure andstrength to the implant 1, also provide closed loops.

Indeed, the different windings 10A-10D are still interconnected toensure, once the device is released, full and circular lesions in theheart, more specifically in the atria, more specifically in the left andright atrium, more specifically in the antrum or ostium of the pulmonaryveins.

In FIG. 4 the implant shows longitudinal metal beads 11 that are outwardbending, and that still show several interconnections between them, toultimately form a metal cage.

An implant 1 according to the present invention may comprise portionsmade of different metal alloys with optionally different ferromagneticproperties and/or absorption coefficients, with specific response toalternating magnetic fields.

Alternatively, the basic structure of the implant 1 may be made of oneand the same material, which may be provided of coating portions withvarying properties.

The embodiment illustrated in FIG. 5 shows an implant conceived as aspirally shaped wire 10 of which the diameter gradually goes down alongits longitudinal axis, but where, as opposed to the embodimentrepresented in FIG. 3, the windings 10A-10E, in this case five, aremutually connected by means of bridging upstanding wires 12 which reachfrom the biggest winding 10A up till the smallest winding 10E.

The biggest winding 10A of the implant 1 is built up of a metallic alloywith self-expanding properties, and covered with a layer of a metal thathas minimal ferromagnetic properties 100.

The next winding 10B is built up of the same self-expanding alloy,covered with a layer of material that has a higher rate of absorption ofenergy during the hysteresis phenomenon, and thus with altering magneticfields will reveal different thermal heating properties 200.

The windings 10D and 10E most distal from the biggest winding 10A, to belocated in a portion of the pulmonary vein remote from the heart, isprovided of a layer of material that has still a higher rate ofabsorption of energy during the hysteresis phenomenon 400.

According to another embodiment of the implant 1, a portion of which isschematically represented in FIG. 6, the wire building up the body 2 ofthe implant 1 is composed of different layers, in this case three layersmade of different alloys 15, 16 and 17.

These different alloys are in contact with each other, and depending ondifferent magnetic fields to be applied, they will exhibit differentproperties.

It is clear that alternatively or in combination with the above or otherfeatures, one or more layers can have high thermal isolationcharacteristics, in order to direct heat where needed, and to isolateportions to prevent undesired heating of blood or tissue.

According to another embodiment of the implant 1, a portion of which isschematically represented in FIG. 7, the body 2 is provided ofmicropores 18 at the abluminal side 13 (in contrast with the adluminalside 14) wherein substances are provided.

Such substances may for example be a selection or a composition of oneor more of the following substances:

-   -   ethanol;    -   tetrodotoxin and batrachotoxin;    -   maurotoxin, agitoxin, charybdotoxin, margatoxin, slotoxin,        scyllatoxin or hefutoxin;    -   calciseptine, taicatoxin, calcicludine, or PhTx3;    -   botulinum toxide;    -   cytochalasin D, rapamycin, sirolimus, zotarolimus, everolimus,        paclitaxel;    -   glutamate;    -   isoquinoline;    -   N-methyl-(R)-salsolinol;    -   Beta-carboline derivates.

The micropores 18 are closed when the body is coiled together, forexample prior to the provision in a guiding catheter system, and uponrelease into its site of destination, upon expansion, these micropores18 open so that the substances inside the metal arms of the cage can bereleased.

According to another embodiment of the implant 1, a portion of which isschematically represented in FIG. 8, the body 2 is covered by athermoactive coating 19 which is only activated upon temperatures above35° C. so that the body temperature would trigger activation.

Alternatively, a thermoactive coating 19 can be provided which is onlyactivated upon temperatures above 45° C. so that an external applicationof an energy field would trigger activation. Alternatively, aninsulating material 44 can be provided at the parts of the implant whichcomes into contact with parts of the body which are preferably notheated such as some parts of the vessel wall or the blood. Hereby theparts of the implant which are heated are thermally insulated from e.g.the blood.

The energy field could for example be a remote applied alternatingmagnetic field, heating the body 2 of the implant 1 thanks to ahysteresis effect.

At the said activation temperature, the coating 19 gets absorbed, andthe active component that is residing below the coating 20 is releasedinto the vascular wall.

Note that the elongated shape and/or the expanding forces provide can beconsidered as anchoring means of the implant 1.

Alternatively, hooks or barbs or the like 29 can be provided as in FIG.11 on the outwardly directed portions of the implant 1, providingguaranteed anchoring of the implant 1 once it put in place.

According to still another embodiment, the outer rings or other cagestructures that are fitted into the antrum, or the whole cage may beequipped with structures to increase the solidity of cage immobility, toascertain the fixed position of the implant, to reduce the possibilityof movement of the implant after the implantation.

The method of placing the implant is easy and can be performed ashereafter described.

According to the known practices, a catheter 30 with guidewire 31 isintroduced up till the place where the implant 1 is to be left. This isshown schematically in FIGS. 12 and 13.

Pull-back of the catheter while leaving the implant 1 in position causesthe implant 1 to expand.

As the shape and/or elastic characteristics of the implant 1 is/aresuitably adapted to fit and optionally press against the arterial orvenous structure, for example in the pulmonary vein, the implant 1 isleft in a safe and self-anchoring manner.

After full pullback of the catheter, the implant 1 is fully released.

Alternatively, the well-known balloon expansion can be applied.

An appropriate period can be awaited prior to applying an externalenergy field in order to trigger the triggerable portions of the implant1.

Various consecutive treatments by simply applying an appropriate energyfield can be considered, without the need to perform renewed invasivesurgery, which is the main advantage of the implant and the systemaccording to the present invention.

Furthermore, in case where the implant 1 is provided of varyingsubstructures, each with their own response to an externally appliedenergy field, varying treatments can be considered, for example withincreasing intensity.

Each portion can for example be triggered with a remote appliedalternating magnetic field characterized with a specific frequency.

It is clear that when reference is made to lesions, these may concerntransmural lesions extending up till the exterior wall, and that lesionsmay be continuous, as opposed to discrete or composed partial lesions.In fact, when the invention disclosed in this text is used for thetreatment of AF by PVI, it is preferable that the lesions are continuousand thus form a substantially circumferential band around the vessel'swall, thereby electrically isolating the PV(s) from the left atrium.

The present invention is by no means limited to the embodimentsdescribed by way of example and represented in the accompanyingdrawings; on the contrary, such an implant and system of an implant andexcitation device for the treatment of arterial and venous structuresaccording to the invention can be made in all sorts of shapes anddimensions while still remaining within the scope of the invention.

FIG. 9 shows a circular braided implant 21 in which one circumferentialregion 22 comprises an alloy with a specific Curie temperature and inwhich a second circumferential region 23 comprises an alloy with anotherspecific Curie temperature.

FIG. 10 shows a funnel-shaped braided implant 24 in which onecircumferential region 25 comprises an alloy with a specific Curietemperature, in which a second circumferential region 26 comprises analloy with another specific Curie temperature, and in which a thirdcircumferential region 27 comprises an alloy with still another specificCurie temperature.

FIG. 11 shows a funnel-shaped braided implant 28 with anchoring means 29in the form of small barbs.

FIG. 13 shows how the catheter 30 can be guided through the insertionvein 34, through the right atrium 36, though a hole to the left atrium35 to the pulmonary vein 37. In detail, the ostium 38 and antrum 39 ofthe PV is indicated.

FIG. 14 represents an embodiment of the external energy-providing means42 as it can be used for treating a patient during the ablationprocedure 43.

FIG. 15 shows an implant in place 40 and the ablation region in crosssection 41 in the antrum of the PV.

FIG. 18 shows another embodiment of an implant which has an hour-glassshape 45, whereby near the middle region, where the diameter becomessmaller, a set of heating rings 46 is attached around the hour-glassshaped part of the implant. The heating rings are attached to thehour-glass shaped part in a thermally insulating manner such that littleheat is transferred to the blood stream when the heating rings areheated. Furthermore the heating rings are meant to be completelyseparated from this blood stream, since the hour-glass shaped part maybe covered by a blood-tight tissue and may be clamped into the vessel ator near the implant ends 47 and 48.

FIG. 19 shows an embodiment of an implant comprising a fuse, so that atcertain temperatures, more specific the temperature that is reached toachieve an optimal ablation, between 40 and 80 degrees Celsius, morespecifically between 45 and 60 degrees Celsius, the circuit that may begenerated gets interrupted. This comes from the phenomenon that when animplant, more specifically a metallic implant, more specifically anitinol implant is brought into the alternating magnetic field, anelectrical current is generated through the metal implant itself, thusgenerating accelerated heating by itself (induction and Joule heating).This phenomenon results in extremely rapid heating of the implant, thatcan be stopped by interrupting the electrical current that may runthrough the implant.

This stopping of the current may be caused by a fuse that is mountedwithin the metallic implant, and that for instance may exist of aresistance, that breaks when it is heated above a certain temperature.In this case, the fuse would stop heating up further above a temperatureof 45-60 degrees, more specifically 50-55 degrees. FIG. 19a shows adetailed view of the fuse.

In a different configuration, as shown in FIG. 20, the metal implant canbe build up of memory shape alloys, so that upon heating of the device,the different metallic parts take up another configuration, therebyinterrupting the electrical current that can run through the implant.Details of the on and off position of the switch or fuse are shown inFIGS. 20a and 20b respectively. This different, i.e. open, configurationconsists potentially of the original form of the metal, so that it goesback to its “memory shape”. This is called a “shape memory metal”.

In a still different configuration as shown in FIG. 21 and a detail inFIG. 21a , the implant consists of two different materials, where uponheating the bondage between the two different metals gets interrupted,so to stop the electrical current from running through the implant.

Another addition of this application is that the heating needs to beunidirectional.

The blood needs to be isolated from the heating because of two reasons:first, blood should not be heated because proteins in the blood candenature and form clots, and second, because blood is a huge heatdissipator that may substract too much heat away from the implant, itwould need too much energy to get the ablation region of the implant tothe desired temperature. Therefore, an extensive coating is formedaround the implant, but almost exclusively on the ADLUMINAL side asillustrated in FIG. 22, so that when the implant is heated, no heat isdissipated towards the blood stream.

It is supposed that the present invention is not restricted to any formof realization described previously and that some modifications can beadded to the presented example of fabrication without reappraisal of theappended claims. For example, the present invention has been describedreferring to PVs, but it is clear that the invention can be applied toother vessels for instance.

What is claimed is:
 1. Method for heating one, two or more implantdevices which are suitable to be implanted in one, two or more vessels,comprising the steps of: positioning said one, two or more implantdevices, subsequently in time in a case where two or more implantdevices are to be positioned, in said one, two or more vessels by meansof a sheath and a guidewire, said implant devices each comprising anablation region along at least a portion of their length, said ablationregion subtending at least a substantially complete circumferential bandor a substantially spiraling band, said implant devices effective forablating a signal-blocking path within said vessels by increasing thetemperature of the ablation region of the implant devices uponapplication of energy to said implant devices; retracting the sheath andguidewire; heating the ablation region of said implant devices byexternal energy-providing means which are spatially separated from saidimplant devices wherein said heating occurs after said sheath andguidewire are retracted, and whereby said heating of said implantdevices occurs simultaneously in the case where two or more implantdevices are positioned, and wherein at least one of the implant devicescomprises an anchoring means for anchoring said at least one of theimplant devices within the vessel upon positioning said at least one ofthe implant devices, and wherein said at least one of the implantdevices comprises a thermally isolating connection between the ablationregion and the anchoring device, wherein the thermally isolatingconnection thermally insulates by thin straps or wires attaching theanchoring device to the ablation region.
 2. Method according to claim 1,wherein the temperature of the ablation region of the implant devices isincreased by an electric current running through the implant.
 3. Methodaccording to claim 2, wherein the electric current is interrupted uponreaching an ablation temperature, thereby halting the increase of thetemperature of the ablation regions.
 4. Method according to claim 3,whereby the implant device comprises a fuse or memory shape alloys ortwo different materials to autonomously interrupt the electric currentat the ablation temperature.
 5. Method according to claim 1, whereinheating occurs by external energy-providing means which create atime-varying magnetic field at the position of said implant devices. 6.Method according to claim 1, wherein at least one of said implantdevices comprises a thermoactive coating comprising an activationtemperature between 35° C. and 37° C. so that the body temperature wouldtrigger activation.
 7. Method according to claim 1, wherein at least oneof said implant devices comprises a thermoactive coating comprising anactivation temperature above 45° C. so that activation is triggered onlywhen said ablation region is heated by said external energy-providingmeans.
 8. Method according to claim 1, wherein at least one implantdevice comprises a shape which is adapted for a pulmonary vein. 9.Method according to claim 1, wherein said vessels comprise one or morepulmonary veins and whereby said ablation regions of said implantdevices are adapted for surface contact with said pulmonary veins andsubtending at least a substantially complete circumferential band forablating a signal-blocking path within said pulmonary veins uponapplication of energy to said implant devices.
 10. Method according toclaim 1, wherein at least one implant device comprises a shape which isadapted for a renal artery.
 11. Method according to claim 1, whereinsaid vessels comprise one or more renal arteries and said ablationregions of said implant devices being adapted for surface contact withsaid renal arteries and subtending at least a substantially spiralingband for ablating a signal- blocking path within said renal arteriesupon application of energy to said implant devices.
 12. Method accordingto claim 1, wherein a recovery period is observed prior to heating theablation region of the one or more implant devices by externalenergy-providing means, whereby said recovery period is long enough toallow the implant devices to be incorporated into the vessel's wall andovergrown by bodily tissue.
 13. Method according to claim 1, wherein anattachment period is observed prior to heating the ablation region ofthe one or more implant devices by external energy-providing means,whereby said attachment period is long enough to allow the implantdevices to position themselves and to not move substantially within thevessel.
 14. Method according to claim 1, wherein the step of heating theablation region of the implant devices by external energy-providingmeans, which are spatially separated from the implant device, isperformed repeatedly.
 15. A self-expanding implant device adapted to beimplanted and deployed within a vessel, said implant comprising anablation region along at least a portion of its length, the ablationregion being adapted for surface contact with the vessel and forsubtending at least a substantially complete circumferential band or aspiraling band and said ablation region effective to ablate asignal-blocking path within the vessel by increasing the temperature ofthe ablation region of the implant device upon application of energy tothe implant device wherein the implant further comprises: an anchoringdevice; and a thermally isolating connection between the ablation regionand the anchoring device, wherein the thermally isolating connectionthermally insulates by thin straps or wires attaching the anchoringdevice to the ablation region.
 16. An implant according to claim 15,wherein the implant is configured to stop increasing the temperature ofthe ablation region by interrupting the electric current.
 17. An implantaccording to claim 16, wherein the implant comprises a fuse or memoryshape alloys or two different materials to autonomously interrupt theelectric current at the ablation temperature.
 18. An implant accordingto claim 15, further comprising a thermoactive coating comprising anactivation temperature above 45° C. so that activation is triggered onlywhen said ablation region is heated by external energy-providing means.19. An implant according to claim 15, further comprising a shape whichis adapted for a pulmonary vein.
 20. An implant according to claim 19,wherein said ablation region of said implant device is adapted forsurface contact with a pulmonary vein and for subtending at least asubstantially complete circumferential band.
 21. An implant accordingclaim 15, further comprising a shape which is adapted for a renalartery.
 22. An implant according to claim 21, wherein said ablationregion of said implant device is adapted for surface contact with saidrenal arteries and for subtending at least a substantially spiralingband.
 23. An implant according to claim 15, further comprising a maximalcircumference and a minimal circumference and a ratio between maximaland minimal circumference, whereby said ratio is smaller than 7 andlarger than
 3. 24. An implant according to claim 15, further comprisinga variable circumference along a longitudinal direction of the implant,said circumference varying between at least 36 mm and at most 250 mm.25. An implant according claim 15, further comprising an essentiallycylindrical shape comprising a diameter which is at least 5 mm and atmost 10 mm.
 26. An implant according to claim 15, further comprising adistal portion and a proximal portion, whereby said ablation region islocated within 50% of the implant's total length from the proximalportion.
 27. An implant according to claim 15, further comprising adistal portion and a proximal portion, whereby said ablation region islocated within 15 mm from the proximal portion.
 28. An implant accordingto claim 15, further comprising a distal portion and a proximal portion,whereby said anchoring device is connected to the distal portion.
 29. Asystem comprising two, three, four or more implant devices according toclaim
 15. 30. A system according to claim 29, comprising externalenergy-providing means, which are spatially separated from said implantdevices and able to provide energy to said implant devices forincreasing the temperature of the ablation regions of the implantdevices.
 31. A system according to claim 30, comprising a sheathsuitable for transporting and delivering the two, three, four or moreimplant devices to or near the desired position in the one or morevessels; and a guidewire suitable for sequentially guiding the sheathwith the two, three, four or more implants to the desired position inthe one or more vessels.
 32. A system comprising two, three or fourimplant devices according to claim 15, each of which adapted for acorresponding pulmonary vein.
 33. A system comprising two implantdevices according to claim 15, each of which adapted for a correspondingrenal artery.
 34. A system comprising an implant according to claim 15and external energy-providing means, which are spatially separated fromsaid implant and able to provide energy to said implant for increasingthe temperature of the ablation region of the implant.
 35. A systemcomprising one or more implants according to claim 15, and: a sheathsuitable for transporting and delivering the one or more implants to ornear the desired position in the one or more vessels; and a guidewiresuitable for sequentially guiding the sheath with the one or moreimplants to the desired position in the one or more vessels.